Despite many large randomised trials assessing adjuvant endocrine treatment for postmenopausal breast cancer patients, the optimal endocrine strategy remains unknown. Neoadjuvant endocrine studies provide the opportunity to model an appropriate study design in a more expeditious manner. Several large adjuvant trials are exploring sequential aromatase inhibitor (AI) strategies. The present study compared the effect of two sequences of AI use – steroidal (exemestane (E)) and nonsteroidal (anastrozole (A)) – on serological and pathological biomarkers, when given in the neoadjuvant setting to patients with locally advanced breast cancer.

Thirty postmenopausal women with estrogen and/or progesterone receptor-positive disease were randomised to receive either E followed by A (E→A group) or A followed by E (A→E group). Each agent was given for 8 weeks. Serum estrone sulfate, and estradiol levels, as well as intratumoral Ki67 were evaluated at baseline, 8 weeks, and 16 weeks. Clinical response, patient preference, and quality of life were also assessed.

Despite rapid falls in sex steroid levels with AI use, there was no difference in estradiol, estrone sulfate or Ki67 levels between groups. There was no significant difference in toxicities, or in quality of life scores. Overall clinical response rate was 68% and clinical benefit was 93%. There was a trend towards improved clinical response in the A→E group. The majority of patients expressed a preference for treatment.

Neither sequence of steroidal or nonsteroidal AI appears to offer a significant advantage over the other. A trend towards improved clinical response in patients treated with A→E is hypothesis-generating and needs confirmation in larger trials.